PTN6_MOUSE
ID PTN6_MOUSE Reviewed; 595 AA.
AC P29351; O35128; Q63872; Q63873; Q63874; Q921G3; Q9QVA6; Q9QVA7; Q9QVA8;
AC Q9R0V6;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2002, sequence version 2.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=Tyrosine-protein phosphatase non-receptor type 6;
DE EC=3.1.3.48;
DE AltName: Full=70Z-SHP;
DE AltName: Full=Hematopoietic cell protein-tyrosine phosphatase;
DE AltName: Full=PTPTY-42;
DE AltName: Full=Protein-tyrosine phosphatase 1C;
DE Short=PTP-1C;
DE AltName: Full=SH-PTP1;
DE Short=SHP-1;
GN Name=Ptpn6; Synonyms=Hcp, Hcph, Ptp1C;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=DBA/2J;
RX PubMed=1732748; DOI=10.1128/mcb.12.2.836-846.1992;
RA Yi T., Cleveland J.L., Ihle J.N.;
RT "Protein tyrosine phosphatase containing SH2 domains: characterization,
RT preferential expression in hematopoietic cells, and localization to human
RT chromosome 12p12-p13.";
RL Mol. Cell. Biol. 12:836-846(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1373816; DOI=10.1128/mcb.12.5.2396-2405.1992;
RA Matthews R.J., Bowne D.B., Flores E., Thomas M.L.;
RT "Characterization of hematopoietic intracellular protein tyrosine
RT phosphatases: description of a phosphatase containing an SH2 domain and
RT another enriched in proline-, glutamic acid-, serine-, and threonine-rich
RT sequences.";
RL Mol. Cell. Biol. 12:2396-2405(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS MOTHEATEN AND VIABLE MOTHEATEN.
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
RX PubMed=8324828; DOI=10.1016/0092-8674(93)90369-2;
RA Schultz L.D., Schweitzer P.A., Rajan T.V., Yi T., Ihle J.N., Matthews R.J.,
RA Thomas M.L., Beier D.R.;
RT "Mutations at the murine motheaten locus are within the hematopoietic cell
RT protein-tyrosine phosphatase (Hcph) gene.";
RL Cell 73:1445-1454(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3).
RX PubMed=9445485;
RA Ansari-Lari M.A., Oeltjen J.C., Schwartz S., Zhang Z., Muzny D.M., Lu J.,
RA Gorrell J.H., Chinault A.C., Belmont J.W., Miller W., Gibbs R.A.;
RT "Comparative sequence analysis of a gene-rich cluster at human chromosome
RT 12p13 and its syntenic region in mouse chromosome 6.";
RL Genome Res. 8:29-40(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), AND SUBUNIT.
RC STRAIN=C3H/HeJ; TISSUE=Adrenal gland;
RX PubMed=10419485; DOI=10.1074/jbc.274.31.21725;
RA Martin A., Tsui H.W., Shulman M.J., Isenman D., Tsui F.W.;
RT "Murine SHP-1 splice variants with altered Src homology 2 (SH2) domains.
RT Implications for the SH2-mediated intramolecular regulation of SHP-1.";
RL J. Biol. Chem. 274:21725-21734(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 54-68; 128-135; 137-151; 242-252; 278-285; 293-308 AND
RP 373-382, AND PHOSPHORYLATION.
RX PubMed=1385421; DOI=10.1016/s0021-9258(18)35855-1;
RA Yeung Y.-G., Berg K.L., Pixley F.J., Angeletti R.H., Stanley E.R.;
RT "Protein tyrosine phosphatase-1C is rapidly phosphorylated in tyrosine in
RT macrophages in response to colony stimulating factor-1.";
RL J. Biol. Chem. 267:23447-23450(1992).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 342-451, AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Myeloid leukemia cell;
RX PubMed=1932742;
RA Yi T., Cleveland J.L., Ihle J.N.;
RT "Identification of novel protein tyrosine phosphatases of hematopoietic
RT cells by polymerase chain reaction amplification.";
RL Blood 78:2222-2228(1991).
RN [9]
RP INTERACTION WITH SIRPA.
RX PubMed=9712903; DOI=10.1074/jbc.273.35.22719;
RA Veillette A., Thibaudeau E., Latour S.;
RT "High expression of inhibitory receptor SHPS-1 and its association with
RT protein tyrosine phosphatase SHP-1 in macrophages.";
RL J. Biol. Chem. 273:22719-22728(1998).
RN [10]
RP INTERACTION WITH KIT, FUNCTION IN MODULATING KIT SIGNALING, AND
RP PHOSPHORYLATION.
RX PubMed=9528781; DOI=10.1128/mcb.18.4.2089;
RA Kozlowski M., Larose L., Lee F., Le D.M., Rottapel R., Siminovitch K.A.;
RT "SHP-1 binds and negatively modulates the c-Kit receptor by interaction
RT with tyrosine 569 in the c-Kit juxtamembrane domain.";
RL Mol. Cell. Biol. 18:2089-2099(1998).
RN [11]
RP INTERACTION WITH CEACAM1.
RX PubMed=9867848; DOI=10.1074/jbc.274.1.335;
RA Huber M., Izzi L., Grondin P., Houde C., Kunath T., Veillette A.,
RA Beauchemin N.;
RT "The carboxyl-terminal region of biliary glycoprotein controls its tyrosine
RT phosphorylation and association with protein-tyrosine phosphatases SHP-1
RT and SHP-2 in epithelial cells.";
RL J. Biol. Chem. 274:335-344(1999).
RN [12]
RP FUNCTION, AND INTERACTION WITH LILRB4A.
RX PubMed=10026201; DOI=10.1074/jbc.274.9.5791;
RA Lu-Kuo J.M., Joyal D.M., Austen K.F., Katz H.R.;
RT "gp49B1 inhibits IgE-initiated mast cell activation through both
RT immunoreceptor tyrosine-based inhibitory motifs, recruitment of src
RT homology 2 domain-containing phosphatase-1, and suppression of early and
RT late calcium mobilization.";
RL J. Biol. Chem. 274:5791-5796(1999).
RN [13]
RP INTERACTION WITH LILRB4A, AND MUTAGENESIS OF 30-ARG--ARG-33 AND ARG-136.
RX PubMed=9973385;
RA Wang L.L., Blasioli J., Plas D.R., Thomas M.L., Yokoyama W.M.;
RT "Specificity of the SH2 domains of SHP-1 in the interaction with the
RT immunoreceptor tyrosine-based inhibitory motif-bearing receptor gp49B.";
RL J. Immunol. 162:1318-1323(1999).
RN [14]
RP INTERACTION WITH CD300LF.
RC STRAIN=C57BL/6J;
RX PubMed=14662855; DOI=10.4049/jimmunol.171.12.6541;
RA Chung D.-H., Humphrey M.B., Nakamura M.C., Ginzinger D.G., Seaman W.E.,
RA Daws M.R.;
RT "CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit
RT osteoclast formation.";
RL J. Immunol. 171:6541-6548(2003).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-377 AND TYR-536, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [17]
RP MUTAGENESIS OF ILE-482.
RX PubMed=19419305; DOI=10.1359/jbmr.090417;
RA Babij P., Roudier M., Graves T., Han C.Y., Chhoa M., Li C.M., Juan T.,
RA Morony S., Grisanti M., Li X., Yu L., Dwyer D., Lloyd D.J., Bass M.B.,
RA Richards W.G., Ebeling C., Amato J., Carlson G.;
RT "New variants in the Enpp1 and Ptpn6 genes cause low BMD, crystal-related
RT arthropathy, and vascular calcification.";
RL J. Bone Miner. Res. 24:1552-1564(2009).
RN [18]
RP INTERACTION WITH CEACAM1.
RX PubMed=19948503; DOI=10.1083/jcb.200904150;
RA Mueller M.M., Klaile E., Vorontsova O., Singer B.B., Obrink B.;
RT "Homophilic adhesion and CEACAM1-S regulate dimerization of CEACAM1-L and
RT recruitment of SHP-2 and c-Src.";
RL J. Cell Biol. 187:569-581(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-57, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Liver, Lung, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [20]
RP INTERACTION WITH MILR1.
RX PubMed=20526344; DOI=10.1038/ni.1886;
RA Hitomi K., Tahara-Hanaoka S., Someya S., Fujiki A., Tada H., Sugiyama T.,
RA Shibayama S., Shibuya K., Shibuya A.;
RT "An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-
RT mediated immediate hypersensitivity reactions.";
RL Nat. Immunol. 11:601-607(2010).
RN [21]
RP INTERACTION WITH MPIG6B.
RX PubMed=23112346; DOI=10.1126/scisignal.2002936;
RA Mazharian A., Wang Y.J., Mori J., Bem D., Finney B., Heising S., Gissen P.,
RA White J.G., Berndt M.C., Gardiner E.E., Nieswandt B., Douglas M.R.,
RA Campbell R.D., Watson S.P., Senis Y.A.;
RT "Mice lacking the ITIM-containing receptor G6b-B exhibit
RT macrothrombocytopenia and aberrant platelet function.";
RL Sci. Signal. 5:RA78-RA78(2012).
RN [22]
RP INTERACTION WITH MOESIN/MSN.
RX PubMed=29247647; DOI=10.1016/j.bbrc.2017.12.061;
RA Gomez C.P., Descoteaux A.;
RT "Moesin and myosin IIA modulate phagolysosomal biogenesis in macrophages.";
RL Biochem. Biophys. Res. Commun. 495:1964-1971(2018).
CC -!- FUNCTION: Modulates signaling by tyrosine phosphorylated cell surface
CC receptors such as KIT and the EGF receptor/EGFR. Enhances the
CC inhibition of mast cell activation mediated by the Lilrb4a receptor
CC (PubMed:10026201). The SH2 regions may interact with other cellular
CC components to modulate its own phosphatase activity against interacting
CC substrates. Together with MTUS1, induces UBE2V2 expression upon
CC angiotensin II stimulation. Plays a key role in hematopoiesis.
CC {ECO:0000269|PubMed:10026201, ECO:0000269|PubMed:9528781}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10044};
CC -!- SUBUNIT: Monomer. Interacts with MTUS1 (By similarity). Interacts with
CC MILR1 (tyrosine-phosphorylated) (PubMed:20526344). Interacts with KIT
CC (PubMed:9528781). Interacts with SIRPA/PTPNS1 (PubMed:9712903).
CC Interacts with FCRL2 and FCRL4 (By similarity). Interacts with CD84 (By
CC similarity). Interacts with CD300LF (PubMed:14662855). Interacts with
CC CDK2 (By similarity). Interacts with KIR2DL1; the interaction is
CC enhanced by ARRB2 (By similarity). Interacts (via SH2 1 domain) with
CC ROS1; the interaction is direct and promotes ROS1 dephosphorylation (By
CC similarity). Interacts with EGFR; inhibits EGFR-dependent activation of
CC MAPK/ERK (By similarity). Interacts with LYN (By similarity). Interacts
CC with the tyrosine phosphorylated form of PDPK1 (By similarity).
CC Interacts with CEACAM1 (via cytoplasmic domain); this interaction
CC depends on the monomer/dimer equilibrium and is phosphorylation-
CC dependent (PubMed:19948503, PubMed:9867848). Interacts with MPIG6B (via
CC ITIM motif) (PubMed:23112346). Interacts with KLRI1 and KLRI2 (By
CC similarity). Interacts with moesin/MSN. Interacts with Lilrb4a (when
CC tyrosine phosphorylated); the interaction enhances Lilrb4a-mediated
CC inhibition of mast cell activation (PubMed:10026201, PubMed:9973385).
CC Interacts with CLEC12B (via ITIM motif). {ECO:0000250|UniProtKB:P29350,
CC ECO:0000250|UniProtKB:P81718, ECO:0000269|PubMed:10026201,
CC ECO:0000269|PubMed:19948503, ECO:0000269|PubMed:20526344,
CC ECO:0000269|PubMed:23112346, ECO:0000269|PubMed:29247647,
CC ECO:0000269|PubMed:9528781, ECO:0000269|PubMed:9712903,
CC ECO:0000269|PubMed:9867848, ECO:0000269|PubMed:9973385}.
CC -!- INTERACTION:
CC P29351; Q91YS8: Camk1; NbExp=3; IntAct=EBI-2620699, EBI-911352;
CC P29351; P35329: Cd22; NbExp=5; IntAct=EBI-2620699, EBI-300059;
CC P29351; Q9Z1S8: Gab2; NbExp=2; IntAct=EBI-2620699, EBI-641738;
CC P29351; P42225: Stat1; NbExp=2; IntAct=EBI-2620699, EBI-647118;
CC P29351; B7UM99: tir; Xeno; NbExp=2; IntAct=EBI-2620699, EBI-2504426;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000250}. Note=In
CC neurons, translocates into the nucleus after treatment with angiotensin
CC II. Shuttles between the cytoplasm and nucleus via its association with
CC PDPK1 (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P29351-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P29351-2; Sequence=VSP_005131;
CC Name=3;
CC IsoId=P29351-3; Sequence=VSP_005132, VSP_005133;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in hematopoietic cells.
CC {ECO:0000269|PubMed:1932742}.
CC -!- DOMAIN: The N-terminal SH2 domain functions as an auto-inhibitory
CC domain, blocking the catalytic domain in the ligand-free close
CC conformation. {ECO:0000250}.
CC -!- PTM: Phosphorylated on tyrosine residues. Phosphorylation at Tyr-564
CC enhances phosphatase activity (By similarity). Binding of KITLG/SCF to
CC KIT increases tyrosine phosphorylation. {ECO:0000250,
CC ECO:0000269|PubMed:1385421, ECO:0000269|PubMed:9528781}.
CC -!- DISEASE: Note=Defects in Ptpn6 are the cause of the motheaten (me) or
CC viable motheaten (mev) phenotypes. Mice homozygous for the recessive
CC allelic mutations develop severe defects in hematopoiesis.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC receptor class 2 subfamily. {ECO:0000305}.
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DR EMBL; M68902; AAA37796.1; -; mRNA.
DR EMBL; M90389; AAA40007.1; -; mRNA.
DR EMBL; S63763; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; S63764; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; S63803; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC002397; AAC36009.1; -; Genomic_DNA.
DR EMBL; AC002397; AAC36008.1; -; Genomic_DNA.
DR EMBL; U65955; AAD00152.1; -; Genomic_DNA.
DR EMBL; U65952; AAD00152.1; JOINED; Genomic_DNA.
DR EMBL; U65953; AAD00152.1; JOINED; Genomic_DNA.
DR EMBL; U65954; AAD00152.1; JOINED; Genomic_DNA.
DR EMBL; U65955; AAD00151.1; -; Genomic_DNA.
DR EMBL; U65951; AAD00151.1; JOINED; Genomic_DNA.
DR EMBL; U65952; AAD00151.1; JOINED; Genomic_DNA.
DR EMBL; U65953; AAD00151.1; JOINED; Genomic_DNA.
DR EMBL; U65954; AAD00151.1; JOINED; Genomic_DNA.
DR EMBL; BC012660; AAH12660.1; -; mRNA.
DR CCDS; CCDS39628.1; -. [P29351-1]
DR CCDS; CCDS51908.1; -. [P29351-2]
DR PIR; A44390; A44390.
DR RefSeq; NP_001071173.1; NM_001077705.2. [P29351-2]
DR RefSeq; NP_038573.2; NM_013545.3. [P29351-1]
DR AlphaFoldDB; P29351; -.
DR SMR; P29351; -.
DR BioGRID; 200256; 22.
DR DIP; DIP-41455N; -.
DR ELM; P29351; -.
DR IntAct; P29351; 15.
DR MINT; P29351; -.
DR STRING; 10090.ENSMUSP00000129124; -.
DR CarbonylDB; P29351; -.
DR iPTMnet; P29351; -.
DR PhosphoSitePlus; P29351; -.
DR SwissPalm; P29351; -.
DR EPD; P29351; -.
DR jPOST; P29351; -.
DR MaxQB; P29351; -.
DR PaxDb; P29351; -.
DR PeptideAtlas; P29351; -.
DR PRIDE; P29351; -.
DR ProteomicsDB; 301880; -. [P29351-1]
DR ProteomicsDB; 301881; -. [P29351-2]
DR ProteomicsDB; 301882; -. [P29351-3]
DR Antibodypedia; 728; 1038 antibodies from 49 providers.
DR DNASU; 15170; -.
DR Ensembl; ENSMUST00000004377; ENSMUSP00000004377; ENSMUSG00000004266. [P29351-2]
DR Ensembl; ENSMUST00000112484; ENSMUSP00000108103; ENSMUSG00000004266. [P29351-1]
DR Ensembl; ENSMUST00000171549; ENSMUSP00000129124; ENSMUSG00000004266. [P29351-2]
DR Ensembl; ENSMUST00000174265; ENSMUSP00000133991; ENSMUSG00000004266. [P29351-3]
DR GeneID; 15170; -.
DR KEGG; mmu:15170; -.
DR UCSC; uc009drk.2; mouse. [P29351-1]
DR CTD; 5777; -.
DR MGI; MGI:96055; Ptpn6.
DR VEuPathDB; HostDB:ENSMUSG00000004266; -.
DR eggNOG; KOG0790; Eukaryota.
DR GeneTree; ENSGT00940000159480; -.
DR HOGENOM; CLU_001645_9_10_1; -.
DR InParanoid; P29351; -.
DR OMA; VKIMCEN; -.
DR PhylomeDB; P29351; -.
DR TreeFam; TF351632; -.
DR Reactome; R-MMU-114604; GPVI-mediated activation cascade.
DR Reactome; R-MMU-1433559; Regulation of KIT signaling.
DR Reactome; R-MMU-201556; Signaling by ALK.
DR Reactome; R-MMU-210990; PECAM1 interactions.
DR Reactome; R-MMU-388841; Costimulation by the CD28 family.
DR Reactome; R-MMU-389948; PD-1 signaling.
DR Reactome; R-MMU-432142; Platelet sensitization by LDL.
DR Reactome; R-MMU-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-MMU-5690714; CD22 mediated BCR regulation.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-877300; Interferon gamma signaling.
DR Reactome; R-MMU-912526; Interleukin receptor SHC signaling.
DR Reactome; R-MMU-912694; Regulation of IFNA/IFNB signaling.
DR Reactome; R-MMU-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR BioGRID-ORCS; 15170; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Ptpn6; mouse.
DR PRO; PR:P29351; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P29351; protein.
DR Bgee; ENSMUSG00000004266; Expressed in granulocyte and 169 other tissues.
DR ExpressionAtlas; P29351; baseline and differential.
DR Genevisible; P29351; MM.
DR GO; GO:0042105; C:alpha-beta T cell receptor complex; IDA:MGI.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0050839; F:cell adhesion molecule binding; IPI:UniProtKB.
DR GO; GO:0046703; F:natural killer cell lectin-like receptor binding; ISO:MGI.
DR GO; GO:0004726; F:non-membrane spanning protein tyrosine phosphatase activity; IBA:GO_Central.
DR GO; GO:0140031; F:phosphorylation-dependent protein binding; ISO:MGI.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:ARUK-UCL.
DR GO; GO:0042169; F:SH2 domain binding; IDA:MGI.
DR GO; GO:0017124; F:SH3 domain binding; IDA:MGI.
DR GO; GO:0005001; F:transmembrane receptor protein tyrosine phosphatase activity; ISS:UniProtKB.
DR GO; GO:0033277; P:abortive mitotic cell cycle; IMP:MGI.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; ISS:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:MGI.
DR GO; GO:1905867; P:epididymis development; IMP:UniProtKB.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI.
DR GO; GO:0000165; P:MAPK cascade; IMP:MGI.
DR GO; GO:0035855; P:megakaryocyte development; IMP:MGI.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IMP:MGI.
DR GO; GO:0002924; P:negative regulation of humoral immune response mediated by circulating immunoglobulin; IMP:MGI.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IGI:ARUK-UCL.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IMP:MGI.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IMP:MGI.
DR GO; GO:0033007; P:negative regulation of mast cell activation involved in immune response; IDA:UniProtKB.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IMP:MGI.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:MGI.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IMP:MGI.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IGI:ARUK-UCL.
DR GO; GO:0035335; P:peptidyl-tyrosine dephosphorylation; ISO:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IMP:MGI.
DR GO; GO:0070527; P:platelet aggregation; IMP:MGI.
DR GO; GO:0030220; P:platelet formation; IGI:MGI.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; IMP:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:MGI.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:MGI.
DR GO; GO:0045577; P:regulation of B cell differentiation; IMP:MGI.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IGI:MGI.
DR GO; GO:0042098; P:T cell proliferation; IMP:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:MGI.
DR Gene3D; 3.30.505.10; -; 2.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR012152; Tyr_Pase_non-rcpt_typ-6/11.
DR Pfam; PF00017; SH2; 2.
DR Pfam; PF00102; Y_phosphatase; 1.
DR PIRSF; PIRSF000929; Tyr-Ptase_nr_6; 1.
DR PRINTS; PR00700; PRTYPHPHTASE.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00194; PTPc; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SMART; SM00252; SH2; 2.
DR SUPFAM; SSF52799; SSF52799; 1.
DR SUPFAM; SSF55550; SSF55550; 2.
DR PROSITE; PS50001; SH2; 2.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50055; TYR_PHOSPHATASE_PTP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Disease variant; Hydrolase; Nucleus; Phosphoprotein; Protein phosphatase;
KW Reference proteome; Repeat; SH2 domain.
FT CHAIN 1..595
FT /note="Tyrosine-protein phosphatase non-receptor type 6"
FT /id="PRO_0000094759"
FT DOMAIN 4..100
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 110..213
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 244..515
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 536..595
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 554..589
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 453
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160,
FT ECO:0000255|PROSITE-ProRule:PRU10044"
FT BINDING 419
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 453..459
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 500
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P81718"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 64
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P29350"
FT MOD_RES 377
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 536
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 564
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000250|UniProtKB:P29350"
FT VAR_SEQ 1..39
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_005132"
FT VAR_SEQ 1..3
FT /note="MVR -> MLSRG (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_005131"
FT VAR_SEQ 40..44
FT /note="SLSVR -> MLSRG (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_005133"
FT VARIANT 77..99
FT /note="EYYTQQQGILQDRDGTIIHLKYP -> VPRPHIWRAGGVTAAGQGRALD
FT (in motheaten (me))"
FT VARIANT 100..595
FT /note="Missing (in motheaten (me))"
FT MUTAGEN 30..33
FT /note="RPSR->KPSE: Slight reduction in binding to
FT phosphorylated Lilrb4a."
FT /evidence="ECO:0000269|PubMed:9973385"
FT MUTAGEN 136
FT /note="R->K: Abolishes binding to phosphorylated Lilrb4a."
FT /evidence="ECO:0000269|PubMed:9973385"
FT MUTAGEN 482
FT /note="I->F: Mice display a low bone mass density and are
FT associated with osteopenia and elevated inflammatory
FT cytokines."
FT /evidence="ECO:0000269|PubMed:19419305"
FT CONFLICT 240
FT /note="A -> R (in Ref. 1; AAA37796)"
FT /evidence="ECO:0000305"
FT CONFLICT 572
FT /note="K -> Q (in Ref. 1; AAA37796)"
FT /evidence="ECO:0000305"
FT CONFLICT 586
FT /note="E -> D (in Ref. 6; AAH12660)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 595 AA; 67559 MW; CF17300D032638D2 CRC64;
MVRWFHRDLS GPDAETLLKG RGVPGSFLAR PSRKNQGDFS LSVRVDDQVT HIRIQNSGDF
YDLYGGEKFA TLTELVEYYT QQQGILQDRD GTIIHLKYPL NCSDPTSERW YHGHISGGQA
ESLLQAKGEP WTFLVRESLS QPGDFVLSVL NDQPKAGPGS PLRVTHIKVM CEGGRYTVGG
SETFDSLTDL VEHFKKTGIE EASGAFVYLR QPYYATRVNA ADIENRVLEL NKKQESEDTA
KAGFWEEFES LQKQEVKNLH QRLEGQRPEN KSKNRYKNIL PFDHSRVILQ GRDSNIPGSD
YINANYVKNQ LLGPDENSKT YIASQGCLDA TVNDFWQMAW QENTRVIVMT TREVEKGRNK
CVPYWPEVGT QRVYGLYSVT NSREHDTAEY KLRTLQISPL DNGDLVREIW HYQYLSWPDH
GVPSEPGGVL SFLDQINQRQ ESLPHAGPII VHCSAGIGRT GTIIVIDMLM ESISTKGLDC
DIDIQKTIQM VRAQRSGMVQ TEAQYKFIYV AIAQFIETTK KKLEIIQSQK GQESEYGNIT
YPPAVRSAHA KASRTSSKHK EEVYENVHSK SKKEEKVKKQ RSADKEKNKG SLKRK
